Calcium sulfate, also known as Plaster of Paris, is known to be an osteoconductive material, and is used in various forms to fill bone voids and increase osteogenesis. Applicant Wright Medical Technology, Inc. is a leading manufacturer of calcium sulfate-based bone repair materials (OSTEOSET® pellets; ALLOMATRIX® bone putty; MIIG® injectable bone putty). When calcium sulfate hemihydrate (CaSO4.1/2H2O) is mixed with water, it forms a paste, which soon crystallizes into a solid form, calcium sulfate di-hydrate (CaSO4.2H2O). Although the crystalline form of calcium sulfate is relatively hard, it is also brittle and lacks sufficient compaction strength to serve as a load bearing structure in prosthetic implants. Perhaps for this reason, little effort has been made to incorporate calcium sulfate into implants. Instead, calcium sulfate is typically used as an adjunct to an implant procedure, such as to fill bone voids around an implant. For example, U.S. Pat. No. 5,147,403 (Gitelis), which is incorporated herein by reference, is directed to the problem of filling gaps between an implantable prosthesis and the patient's bone. Gitelis teaches solving the problem by applying calcium sulfate in free-flowing form to the receiving surface of the host bone and then seating the prosthesis in the receiving surface, such that the calcium sulfate fills one or more of the gaps resulting between the prosthesis and the host bone. Gitellis does not teach or suggest using a porous coating on the implant, filling a porous coating with calcium sulfate, nor wiping off excess coating to preserve a load bearing surface.
Implants having a porous surface configured to promote bone in-growth are well known. Porous implants have the advantage of being implantable without the use of bone cement. Various types of porous implant surfaces have been developed. U.S. Pat. No. 3,605,123 (Hahn), which is incorporated herein by reference, discloses a dense metal base and an overlying highly porous metallic layer which permits growth of bone tissue into the pores. U.S. Pat. No. 3,855,638 (Pilliar), which is incorporated herein by reference, describes a prosthetic device comprised of a solid metallic material substrate and a porous coating of metallic material adhered to and extending over a portion of the substrate surface. The porous coating consists of a plurality of small ball-shaped metallic particles that are bonded together at their points of contact with each other and the substrate to define a plurality of connected, interstitial pores uniformly distributed throughout the coating. The porous coating is suitable for ingrowth of boney tissue into the porous coating.
U.S. Pat. No. 3,906,550 (Rostoker, et al), which is incorporated herein by reference, describes a prosthetic device which includes a porous fiber metal structure formed from substantially sinusoidally shaped fiber strands. The points of contact between the fibers are metallurgically bonded by a sintering process. This fiber metal structure provides at least a portion of the surface of the prosthetic device adjacent to the skeletal structure to enable bone and soft tissue growth into the fiber metal structure.
U.S. Pat. No. 4,715,860 (Amstutz et al.), which is incorporated herein by reference, describes an acetabular cup for an artificial hip joint that is provided with a right cylindrical portion and chamfered dome which is of porous titanium or other suitable material, including a coating of either sintered fibers or sintered small particles such as spheres, to encourage early bone ingrowth following force fit insertion of the cup into the acetabulum.
U.S. Pat. No. 4,834,756 (Kenna), which is incorporated herein by reference, describes a metallic bone prosthesis having a porous coating for bone ingrowth or interlocking with bone cement. The porous coating comprises two layers of generally ball-shaped metallic particles bonded together at their points of contact, e.g. by sintering, and defining between them a plurality of connected interstitial pores having an average pore size of from about 350 microns to about 500 microns.
U.S. Pat. Nos. 6,136,229 (Johnson) and 6,296,667 (Johnson), which are incorporated herein by reference, make the following observations concerning metals that can be used to form porous frameworks:                Metals which can be used to form the hard, strong, continuous framework component include titanium, stainless steels, cobalt/chrome alloys, tantalum, titanium-nickel alloys such as Nitinol and other superelastic metal alloys. Reference is made to Itin, et al., “Mechanical Properties and Shape Memory of Porous Nitinol,” Materials Characterization [32] pp. 179-187(1994); Bobyn, et al., “Bone Ingrowth Kinetics and Interface Mechanics of a Porous Tantalum Implant Material,” Transactions of the 43rd Annual Meeting, Orthopaedic Research Society, p. 758, Feb. 9-13, 1997 San Francisco, Calif.; and to Pederson, et al., “Finite Element Characterization of a Porous Tantalum Material for Treatment of A vascular Necrosis,” Transactions of the 43rd Annual Meeting, Orthopaedic Research Society, p. 598 Feb. 9-13, 1997. San Francisco, Calif., the teachings of all of which are incorporated by reference. Metals can be formed into hard, strong, continuous supportive frameworks by a variety of manufacturing procedures including combustion synthesis, plating onto a “foam” substrate, chemical vapor deposition (see U.S. Pat. No. 5,282,861), lost mold techniques (see U.S. Pat. No. 3,616,841), foaming molten metal (see U.S. Pat. Nos. 5,281,251, 3,816,952 and 3,790,365) and replication of reticulated polymeric foams with a slurry of metal powder as described for ceramic powders.        
Incorporation of osteoconductive and osteoinductive materials into the surface of implants is known. However, most prior art uses of osteoconductive implant coatings focus on calcium phosphate, which can form hard crystalline structures such as hydroxyapatite. For example, U.S. Pat. Nos. 6,136,229 (Johnson) and 6,296,667 (Johnson) note:                By and large, metal or ceramic materials that have been proposed for bone substitutes have been of low porosity and have involved substantially dense metals and ceramics with semi-porous surfaces filled or coated with a calcium phosphate based material. The resulting structure has a dense metal or ceramic core and a surface which is a composite of the core material and a calcium phosphate, or a surface which is essentially a calcium phosphate. The bone substitute materials of this type commonly are heavy and dense, and often are significantly stiffer in structure than bone. Reference here is made to U.S. Pat. No. 5,306,673 (Hermansson et al.), U.S. Pat. No. 4,599,085 (Riess et al.), U.S. Pat. No. 4,626,392 (Kondo et al.), and U.S. Pat. No. 4,967,509 (Tamari et al.).        
Prior art methods of providing implants with osteogenic calcium phosphate materials have generally been complex, and therefore expensive. For example U.S. Pat. No. 5,306,673 (Hermansson) discloses a method of manufacturing a composite ceramic material having a high strength combined with bioactive properties when the material is used as a dental or orthopedic implant. The method includes preparing a powder mixture, mainly comprising partly a first powder, which in its used chemical state will constitute a bioinert matrix in the finished material, and partly a second powder, mainly comprising a calcium phosphate-based material. The first powder comprises at least one of the oxides belonging to the group consisting of titanium dioxide (TiO2), zirconium oxide (ZrO2) and aluminum oxide (Al2 O3). The second powder mainly comprises at least one of the compounds hydroxylapatite and tricalcium phosphate. A raw compact is made of the powder mixture. The raw compact is densified through an isostatic pressing in a hot condition (HIP) at a pressure higher than 50 MPa to produce a composite material. The resulting composite material is a matrix that comprises one or several metal oxides of the first powder, and in which hydroxylapatite and/or tricalcium phosphate is evenly dispersed. The invention also relates to a composite ceramic material as well as a body, completely or partially made of this material.
Another example of complexity is provided by U.S. Pat. No. 4,599,085 (Riess et al.), which discloses a bone implant member which is characterized in that the support or carrier material is a biocompatible metal, such as titanium, tantalum, niobium or a similar harmless sintered metal which is capable of bonding with calcium phosphate ceramic without the formation of intermediate reaction products. Reiss discloses that calcium phosphate ceramics which are present as a powder in a finely-dispersed up to lumpy form can be combined with titanium powder of a somewhat similar grain size into a compound material through a pressing or sintering process, which evidences the physical and chemical advantages of the sum of the individual materials. The sintering temperature lies within a range of over 1500° K. (degrees Kelvin) up to 2300° K. in conformance with the intended sintering density of the calcium phosphate support member. The implant member includes, at least at the sides facing towards the bone surface in the implant space within the bone, a surface layer consisting completely of calcium phosphate, particularly tricalcium phosphate. Due to obtained experimental and clinical experiences, the pure calcium phosphate surface layer should have the thickness of about 0.1 to 0.5 mm. the surface layer of pure calcium phosphate is pressed on the implant member through the intermediary of a further pressure-sintering process. The sintered tricalcium phosphate surface layer is homogeneously interconnected with the calcium phosphate particles containing metal-calcium phosphate in the compound material whereas, in the compound material itself, there is present more than one mechanical bond between metal and calcium phosphate, so that the tricalcium phosphate surface layer is present in a fixed bonded formation with the support member.
U.S. Pat. No. 5,108,436 (Chu et al.) discloses methods for incorporating a osteogenic proteins into stress-bearing members: “A number of procedures may be used to combine the stress-bearing member with an osteoinductive composition. The simplest procedure is to coat or dip the stress-bearing member with a solution of OFE, or a suspension containing the osteogenic protein and TGF-beta. Sufficient OFE or suspension of the osteogenic protein and TGF-beta is applied to completely cover the portion of the stress-bearing member to be fixed by bone ingrowth. Alternatively, sufficient amounts of the osteoinductive composition may be applied to completely saturate the stress-bearing member.” (Col. 6, lines 9-19). Chu further states: “The solution of OFE or suspension containing the osteoinductive protein and TGF-beta may be further air-dried or freeze-dried onto the stress-bearing member to provide a dry osteoinductive prosthesis.” (Col. 6, lines 47-51). Chu discloses that the osteogenic protein is will normally be formulated in osteogenically effective amounts with pharmaceutically acceptable solid or fluid carriers. Preferably, the formulations include a matrix that is capable of providing a structure for developing bone and cartilage. Potential matrices may be biodegradable or nonbiodegradable, and may be chemically or biologically defined. Although the Chu invention appears to have been directed toward a collagen carrier, it also mentions the use of calcium sulfate: “Other preferred pharmaceutically acceptable carriers may be materials such as calcium sulfate, hydroxyapatite, tricalcium phosphate, polyorthoesters, polylactic-polyglycolic acid copolymers, bioglass, and the like.” (Col. 6, lines 3-6).
In contrast with calcium phosphate, little effort has been made to incorporate calcium sulfate into implants. Applicant is aware of three examples in U.S. Pat. No. 6,136,029 (Johnson), U.S. Pat. No. 6,296,667 (Johnson) and U.S. P.A.P. 2002/0169066 (Cassidy et al.), all of which are incorporated herein by reference (and all of which are owned by applicant, Wright Medical). Each of these patent documents discloses the general concept of providing a porous structure having an osteoconductive component, as well as providing the porous osteoconductive component on the surface of an implant. The porous structure can be of metal. For example, the Cassidy patent application states, at ¶¶48-49: “These materials [i.e. of the porous structure] can include bioactive ceramic materials (e.g., hydroxyapatite, tricalcium phosphate, and fluoroapatite), ceramics (e.g., alumina and zirconia), metals and combinations of these materials. . . . Metals that can be used to form the porous element include titanium, stainless steels, cobalt/chromium alloys, tantalum, titanium-nickel alloys such as Nitinol and other superelastic metal alloys.” The Johnson references state: “Metals which can be used to form the hard, strong, continuous framework component include titanium, stainless steels, cobalt/chrome alloys, tantalum, titanium-nickel alloys such as Nitinol and other superelastic metal alloys.” Each of these patent documents mentions calcium sulfate, but only in passing. The Johnson patents make only one reference to calcium sulfate, as follows: “Examples of ceramic materials for the osteoconductive portion include calcium phosphates (e.g., hydroxyapatite, fluorapatite, and tricalcium phosphate and mixtures thereof), bioactive glasses, osteoconductive cements, and compositions containing calcium sulfate or calcium carbonate.” The Cassidy application makes only one reference to calcium sulfate, as follows: “For medical applications, osteoconductive and osteoinductive materials can be included with both the porous and dense elements. The osteoconductive and osteoinductive materials that are appropriate for use in the present invention are biologically acceptable and include such osteoconductive materials as collagen and the various forms of calcium phosphates including hydroxyapatite; tricalcium phosphate; and fluoroapatite, bioactive glasses, osteoconductive cements, and compositions containing calcium sulfate or calcium carbonate . . .” Thus, the Johnson and Cassidy references do not specifically teach the use of bulk form calcium sulfate hemi-hydrate, applying the calcium sulfate in the form of an aqueous solution, nor wiping to remove excess calcium sulfate.
As far as the applicant can determine, the only instance in which a wiping operation has been applied to a coating on an implantable device appears in U.S. PAP 2001/0014717 A1 (Hossainy) and its family members. U.S. PAP 2001/0014717 A1 states, at ¶0083: “Application of the composition can be by any conventional method, such as by spraying the composition onto the prosthesis or immersing the prosthesis in the composition. Operations such as wiping, centrifugation, blowing, or other web clearing acts can also be performed to achieve a more uniform coating. Briefly, wiping refers to physical removal of excess coating from the surface of the stent; . . .” The Houssainy application is directed toward stents. The application does not discuss porosity or pores, and likewise provides no teaching concerning using a wiping process to preserve a load bearing surface of a porous layer. The Houssainy application mentions calcium sulfate only once, in ¶0073, as being one of dozens of “particles” suitable for use in a composition for forming a rate reducing membrane. Houssainy states that “particles of inorganic or organic type are added to the blend. The particles should be dispersed in the blend. Dispersed is defined as the particles being present as individual particles, not agglomerates or flocs.” (¶ 0071) Houssainy's definition of “dispersed” thus excludes use of calcium sulfate in the crystalline calcium sulfate hemi-hydrate form contemplated by the present invention.
As mentioned above, applicant Wright Medical Technology, Inc. is a leading manufacturer of calcium sulfate-based bone repair materials. Applicant has discovered that at least one of its products, OSTEOSET® resorbable bead kit, can be used in the efficient process describe below to provide an implant that has both a porous load bearing surface and an impregnated bioresorbable calcium sulfate layer. There is thus a need for a method of preparing or manufacturing a coated implant having the following characteristics and advantages over the prior art.